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Varying FSH levels and their impact on IVF

Should FSH test be repeated over and over again prior to IVF ?

The serum concentration of FSH (follicle stimulating hormone) on day 3 of the menstrual cycle has been the standard test to give some indication of the number of eggs remaining in the ovary (ovarian reserve). Ovarian reserve decreases with age, often alarmingly so after the age of 35, determines the response of the ovary to stimulation and, indirectly, hints at the prognosis for pregnancy.

FSH originates in the pituitary gland at the base of the brain and is released into the blood stream in order to stimulate the growth of follicles containing eggs and so is vital to achieve ovulation. FSH also encourages the production of hormones from the ovary, mainly estrogens and inhibin. These two hormones feed back to the pituitary and regulate the amount of FSH that is released. With increasing female age and the consequent depletion of the number of eggs in their follicles, the production of estrogen and, particularly, inhibin decreases and, in response, the levels of FSH increase. This can be seen as a compensatory mechanism to try and keep the ovary going. This is the reason why levels of FSH are used as a test of ovarian reserve; the higher the FSH, the lower the ovarian reserve or number of eggs remaining. The nearer the approaching menopause, the higher will be the levels of FSH and the lower the chances of becoming pregnant. Rather than predicting the chances of pregnancy, the FSH level is better at predicting the response of the ovary to stimulation in treatment such as in-vitro fertilization (IVF).

The ideal time to sample blood for FSH levels is on day 3 of a cycle although day 2-4 will probably suffice. Any testing outside of these days is irrelevant. When used as a screening test for ovarian reserve, levels of estradiol should also be measured. A combination of high FSH (>15 IU/L) and high estradiol levels (>200 pmol/L) are usually bad news. In patients with an age less than 40 years, high FSH levels are a less reliable indicator of the chances for pregnancy.

As the FSH concentration around day 3 of the cycle is dependent on a number of hormonal interactions, it often varies from cycle to cycle and this variation of levels may be confusing. Apparent ‘rejuvenation’ of the ovary according to a transient decrease of FSH levels following high values in a previous cycle can be misleading as it has been reported that the highest FSH value measured is the one that most accurately predicts the ovarian reserve. Although the FSH test has long been used routinely, it is now being superseded by testing for blood levels of anti-Mullerian hormone (AMH) and by the antral follicle count on ultrasound examination.

Amit Shah, Anil Gudi & Prof Homburg

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